Pediatric Cancer Genome Project

St. Jude Children’s Research Hospital and Washington University School of Medicine in St. Louis, announced on January 25, 2010 an unprecedented effort to identify the genetic changes that give rise to some of the world’s deadliest childhood cancers. The team joined forces to decode the genomes of more than 600 childhood cancer patients, who contributed tumor samples for this historic effort.

The St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project was the largest investment at the time—estimated to cost $65 million over three years—aimed at understanding the genetic origins of childhood cancers. Scientists involved in the project sequenced the entire genomes of both normal and cancer cells from each patient, comparing differences in the DNA to identify genetic mistakes that lead to cancer. Kay Jewelers, a long-standing supporter of St. Jude Children’s Research Hospital, committed to provide $20 million as lead sponsor of this project.

Foundation for future research

St. Jude is home to one of the world’s largest and most complete repositories of biological information about childhood cancer. The collection dates to the 1970s and includes tumor, bone marrow, blood and other biological samples. These samples are essential to understand the origins of cancer. The tissue bank has also helped St. Jude scientists develop the experimental models expected to be important for determining which mutations drive cancer’s development and spread.

The collaboration focused on childhood leukemias, brain tumors and tumors of bone, muscle and other connective tissues called sarcomas. St. Jude provided DNA from tumor and normal tissues of patients, Washington University’s McDonnell Genome Institute performed the whole genome sequencing, and both participated in validation sequencing. Researchers at both institutions collaborated to analyze the data and make the information publicly available. Prior research by this group and others indicates that the many genetic abnormalities in childhood cancers will differ from those found in adult cancers.

Decoding complete cancer genome

Scientists at Washington University’s McDonnell Genome Institute pioneered whole-genome sequencing of cancer patients’ genomes. In 2008, they became the first to decode the complete genome of a cancer patient – a woman with leukemia – and trace her disease to its genetic roots. They have since sequenced the genomes of additional cancer patients, including those with breast, lung and ovarian tumors and glioblastoma, a type of brain tumor. These studies have identified intriguing and unexpected genetic connections between patients with different types of cancer that likely would not have been discovered using conventional approaches.

Earlier research to identify cancer mutations has typically focused only on the few hundred genes already suspected of being involved in the disease. While a few recent studies have involved sequencing the 20,000 or so protein-coding genes in the genome, the whole-genome approach involved in this collaboration provided a more detailed and complete picture of all the mutations involved in a patient’s cancer by examining both the protein-coding genes and the long stretches of DNA between genes, which may influence the ways the genes work. Such complete genomic sequencing was possible because of advances that have made the technology faster and far less expensive.

Researchers involved in the project also investigated how pediatric cancer is influenced by variations in the genome, including epigenetic changes, which alter the expression of genes but not the genes themselves. They used DNA sequencing data to identify genetic markers that can help physicians decide the best treatment options for cancer patients, based on the genetic profile of their tumors.

A track record of innovation

The project’s scope and design reflects the philosophies and talents of the institutions involved. St. Jude and Washington University have a history of scientific collaboration and a track record of innovation in patient care. They also share a commitment to excellence and openness in research. The pediatric genome project includes a public database where validated information is shared with the international scientific community, with the goal of accelerating progress against childhood cancer. While great progress has been made in treating childhood cancer, it is still the leading cause of death from disease among U.S. children over one year of age, and cure rates for some childhood cancers remain below 50 percent.

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer and other catastrophic diseases. Ranked the No. 1 pediatric cancer hospital by Parents magazine, St. Jude is the first and only NCI-designated Comprehensive Cancer Center devoted solely to children, and has treated children from all 50 states and from around the world. St. Jude has developed research protocols that helped push overall survival rates for childhood cancer from less than 20 percent when the hospital opened to almost 80 percent today. St. Jude is the national coordinating center for the Pediatric Brain Tumor Consortium and the Childhood Cancer Survivor Study. In addition to pediatric cancer research, St. Jude is also a leader in sickle cell disease research and is a globally prominent research center for influenza.

Founded in 1962 by the late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world, publishing more research articles than any other pediatric cancer research center in the United States. St. Jude treats over 5,400 patients each year and is the only pediatric cancer research center where families never pay for treatment not covered by insurance. St. Jude is financially supported by thousands of individual donors, organizations and corporations without which the hospitals’ work would not be possible. For more information, visit St. Jude’s website.

Washington University School of Medicine and the McDonnell Genome Institute

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation. Through its affiliations with Barnes-Jewish Hospital, and St. Louis Children’s Hospital, named among the nation’s elite pediatric hospitals by U.S. News & World Report, the School of Medicine is linked to BJC HealthCare. Washington University and Barnes-Jewish Hospital are also home to the Siteman Cancer Center, a federally designated Comprehensive Cancer Center. For more information, visit the School of Medicine’s website.

The McDonnell Genome Institute at Washington University is a leader in genomics research as it applies to the study of biology, human disease and the field of personalized medicine. Founded in 1993, The McDonnell Genome Institute focuses on cancer genomics, the genomics of heritable diseases, microbial and pathogen genomics, as well as novel sequencing and evolutionary genomics.